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Protein

Lysine-specific demethylase 6A

Gene

KDM6A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code (PubMed:17851529, PubMed:17713478, PubMed:17761849). Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-27' (PubMed:17851529, PubMed:17713478, PubMed:17761849). Plays a central role in regulation of posterior development, by regulating HOX gene expression (PubMed:17851529). Demethylation of 'Lys-27' of histone H3 is concomitant with methylation of 'Lys-4' of histone H3, and regulates the recruitment of the PRC1 complex and monoubiquitination of histone H2A (PubMed:17761849). Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression (By similarity).By similarity4 Publications

Miscellaneous

Escapes X chromosome inactivation.

Cofactori

Protein has several cofactor binding sites:

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi1146Iron1 Publication1
Metal bindingi1148Iron1 Publication1
Metal bindingi1226Iron1 Publication1
Metal bindingi1331Zinc1 Publication1
Metal bindingi1334Zinc1 Publication1
Metal bindingi1358Zinc1 Publication1
Metal bindingi1361Zinc1 Publication1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChromatin regulator, Dioxygenase, Oxidoreductase
LigandIron, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-3214842 HDMs demethylate histones
R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Lysine-specific demethylase 6A (EC:1.14.11.-4 Publications)
Alternative name(s):
Histone demethylase UTX
Ubiquitously-transcribed TPR protein on the X chromosome
Ubiquitously-transcribed X chromosome tetratricopeptide repeat protein
Gene namesi
Name:KDM6A
Synonyms:UTX
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000147050.14
HGNCiHGNC:12637 KDM6A
MIMi300128 gene
neXtProtiNX_O15550

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Kabuki syndrome 2 (KABUK2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA congenital mental retardation syndrome with additional features, including postnatal dwarfism, a peculiar facies characterized by long palpebral fissures with eversion of the lateral third of the lower eyelids, a broad and depressed nasal tip, large prominent earlobes, a cleft or high-arched palate, scoliosis, short fifth finger, persistence of fingerpads, radiographic abnormalities of the vertebrae, hands, and hip joints, and recurrent otitis media in infancy.
See also OMIM:300867

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1146H → A: Abolishes histone demethylase activity. 3 Publications1

Keywords - Diseasei

Mental retardation

Organism-specific databases

DisGeNETi7403
GeneReviewsiKDM6A
MalaCardsiKDM6A
MIMi300867 phenotype
OpenTargetsiENSG00000147050
Orphaneti2322 Kabuki syndrome
PharmGKBiPA37262

Chemistry databases

ChEMBLiCHEMBL2069164
GuidetoPHARMACOLOGYi2684

Polymorphism and mutation databases

BioMutaiKDM6A

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001064091 – 1401Lysine-specific demethylase 6AAdd BLAST1401

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei519Omega-N-methylarginineBy similarity1
Modified residuei549Omega-N-methylarginineBy similarity1
Modified residuei769PhosphoserineCombined sources1
Modified residuei827PhosphothreonineBy similarity1
Modified residuei829PhosphoserineCombined sources1

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiO15550
MaxQBiO15550
PaxDbiO15550
PeptideAtlasiO15550
PRIDEiO15550
ProteomicsDBi48752

PTM databases

iPTMnetiO15550
PhosphoSitePlusiO15550

Expressioni

Gene expression databases

BgeeiENSG00000147050 Expressed in 223 organ(s), highest expression level in kidney
CleanExiHS_UTX
ExpressionAtlasiO15550 baseline and differential
GenevisibleiO15550 HS

Organism-specific databases

HPAiHPA000568
HPA001165
HPA002111

Interactioni

Subunit structurei

Interacts with TLE1 (By similarity). Component of the MLL2/3 complex (also named ASCOM complex), at least composed of KMT2D/MLL2 or KMT2C/MLL3, ASH2L, RBBP5, WDR5, NCOA6, DPY30, KDM6A (or KDM6B), PAXIP1/PTIP, PAGR1 and alpha- and beta-tubulin (PubMed:17500065, PubMed:17713478). Interacts with SUPT6H. Interacts with SMARCA4 (By similarity).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113246, 35 interactors
CORUMiO15550
DIPiDIP-46192N
IntActiO15550, 19 interactors
MINTiO15550
STRINGi9606.ENSP00000367203

Chemistry databases

BindingDBiO15550

Structurei

Secondary structure

11401
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO15550
SMRiO15550
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati93 – 126TPR 1Add BLAST34
Repeati130 – 163TPR 2Add BLAST34
Repeati170 – 199TPR 3Add BLAST30
Repeati205 – 238TPR 4Add BLAST34
Repeati250 – 283TPR 5Add BLAST34
Repeati284 – 317TPR 6Add BLAST34
Repeati318 – 351TPR 7Add BLAST34
Repeati352 – 385TPR 8Add BLAST34
Domaini1095 – 1258JmjCPROSITE-ProRule annotationAdd BLAST164

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 1095Interaction with SUPT6HBy similarityAdd BLAST1095

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi9 – 17Poly-Ala9

Sequence similaritiesi

Belongs to the UTX family.Curated

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG1124 Eukaryota
KOG1246 Eukaryota
COG0457 LUCA
GeneTreeiENSGT00410000025758
InParanoidiO15550
KOiK11447
PhylomeDBiO15550
TreeFamiTF317405

Family and domain databases

Gene3Di1.25.40.10, 2 hits
InterProiView protein in InterPro
IPR003347 JmjC_dom
IPR029516 KDM6C
IPR013026 TPR-contain_dom
IPR011990 TPR-like_helical_dom_sf
IPR019734 TPR_repeat
PANTHERiPTHR14017:SF9 PTHR14017:SF9, 2 hits
PfamiView protein in Pfam
PF02373 JmjC, 1 hit
PF13181 TPR_8, 1 hit
SMARTiView protein in SMART
SM00558 JmjC, 1 hit
SM00028 TPR, 6 hits
SUPFAMiSSF48452 SSF48452, 2 hits
PROSITEiView protein in PROSITE
PS51184 JMJC, 1 hit
PS50005 TPR, 7 hits
PS50293 TPR_REGION, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 9 potential isoforms that are computationally mapped.Show allAlign All

O15550-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MKSCGVSLAT AAAAAAAFGD EEKKMAAGKA SGESEEASPS LTAEEREALG
60 70 80 90 100
GLDSRLFGFV RFHEDGARTK ALLGKAVRCY ESLILKAEGK VESDFFCQLG
110 120 130 140 150
HFNLLLEDYP KALSAYQRYY SLQSDYWKNA AFLYGLGLVY FHYNAFQWAI
160 170 180 190 200
KAFQEVLYVD PSFCRAKEIH LRLGLMFKVN TDYESSLKHF QLALVDCNPC
210 220 230 240 250
TLSNAEIQFH IAHLYETQRK YHSAKEAYEQ LLQTENLSAQ VKATVLQQLG
260 270 280 290 300
WMHHTVDLLG DKATKESYAI QYLQKSLEAD PNSGQSWYFL GRCYSSIGKV
310 320 330 340 350
QDAFISYRQS IDKSEASADT WCSIGVLYQQ QNQPMDALQA YICAVQLDHG
360 370 380 390 400
HAAAWMDLGT LYESCNQPQD AIKCYLNATR SKSCSNTSAL AARIKYLQAQ
410 420 430 440 450
LCNLPQGSLQ NKTKLLPSIE EAWSLPIPAE LTSRQGAMNT AQQNTSDNWS
460 470 480 490 500
GGHAVSHPPV QQQAHSWCLT PQKLQHLEQL RANRNNLNPA QKLMLEQLES
510 520 530 540 550
QFVLMQQHQM RPTGVAQVRS TGIPNGPTAD SSLPTNSVSG QQPQLALTRV
560 570 580 590 600
PSVSQPGVRP ACPGQPLANG PFSAGHVPCS TSRTLGSTDT ILIGNNHITG
610 620 630 640 650
SGSNGNVPYL QRNALTLPHN RTNLTSSAEE PWKNQLSNST QGLHKGQSSH
660 670 680 690 700
SAGPNGERPL SSTGPSQHLQ AAGSGIQNQN GHPTLPSNSV TQGAALNHLS
710 720 730 740 750
SHTATSGGQQ GITLTKESKP SGNILTVPET SRHTGETPNS TASVEGLPNH
760 770 780 790 800
VHQMTADAVC SPSHGDSKSP GLLSSDNPQL SALLMGKANN NVGTGTCDKV
810 820 830 840 850
NNIHPAVHTK TDNSVASSPS SAISTATPSP KSTEQTTTNS VTSLNSPHSG
860 870 880 890 900
LHTINGEGME ESQSPMKTDL LLVNHKPSPQ IIPSMSVSIY PSSAEVLKAC
910 920 930 940 950
RNLGKNGLSN SSILLDKCPP PRPPSSPYPP LPKDKLNPPT PSIYLENKRD
960 970 980 990 1000
AFFPPLHQFC TNPNNPVTVI RGLAGALKLD LGLFSTKTLV EANNEHMVEV
1010 1020 1030 1040 1050
RTQLLQPADE NWDPTGTKKI WHCESNRSHT TIAKYAQYQA SSFQESLREE
1060 1070 1080 1090 1100
NEKRSHHKDH SDSESTSSDN SGRRRKGPFK TIKFGTNIDL SDDKKWKLQL
1110 1120 1130 1140 1150
HELTKLPAFV RVVSAGNLLS HVGHTILGMN TVQLYMKVPG SRTPGHQENN
1160 1170 1180 1190 1200
NFCSVNINIG PGDCEWFVVP EGYWGVLNDF CEKNNLNFLM GSWWPNLEDL
1210 1220 1230 1240 1250
YEANVPVYRF IQRPGDLVWI NAGTVHWVQA IGWCNNIAWN VGPLTACQYK
1260 1270 1280 1290 1300
LAVERYEWNK LQSVKSIVPM VHLSWNMARN IKVSDPKLFE MIKYCLLRTL
1310 1320 1330 1340 1350
KQCQTLREAL IAAGKEIIWH GRTKEEPAHY CSICEVEVFD LLFVTNESNS
1360 1370 1380 1390 1400
RKTYIVHCQD CARKTSGNLE NFVVLEQYKM EDLMQVYDQF TLAPPLPSAS

S
Length:1,401
Mass (Da):154,177
Last modified:September 23, 2008 - v2
Checksum:i9DD7EA6C61E79229
GO

Computationally mapped potential isoform sequencesi

There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087X0R0A0A087X0R0_HUMAN
Lysine-specific demethylase 6A
KDM6A
1,429Annotation score:
F5H6S1F5H6S1_HUMAN
Lysine-specific demethylase 6A
KDM6A
1,332Annotation score:
A0A087WUN6A0A087WUN6_HUMAN
Lysine-specific demethylase 6A
KDM6A
224Annotation score:
F8W8R6F8W8R6_HUMAN
Lysine-specific demethylase 6A
KDM6A
1,384Annotation score:
F5H5V6F5H5V6_HUMAN
Lysine-specific demethylase 6A
KDM6A
1,269Annotation score:
H0Y6I7H0Y6I7_HUMAN
Lysine-specific demethylase 6A
KDM6A
999Annotation score:
H0Y5J3H0Y5J3_HUMAN
Lysine-specific demethylase 6A
KDM6A
1,044Annotation score:
H7C1F1H7C1F1_HUMAN
Lysine-specific demethylase 6A
KDM6A
224Annotation score:
H0Y6V5H0Y6V5_HUMAN
Lysine-specific demethylase 6A
KDM6A
161Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti173L → V in AAC51839 (PubMed:9381176).Curated1
Sequence conflicti173L → V in AAC51840 (PubMed:9381176).Curated1
Sequence conflicti585L → R in AAC51839 (PubMed:9381176).Curated1
Sequence conflicti585L → R in AAC51840 (PubMed:9381176).Curated1
Sequence conflicti601S → N in AAC51839 (PubMed:9381176).Curated1
Sequence conflicti601S → N in AAC51840 (PubMed:9381176).Curated1
Sequence conflicti629E → K in AAC51839 (PubMed:9381176).Curated1
Sequence conflicti629E → K in AAC51840 (PubMed:9381176).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01449230A → T. Corresponds to variant dbSNP:rs6529EnsemblClinVar.1
Natural variantiVAR_067225270I → V in a patient with chronic myelomonocytic leukemia. 1 Publication1
Natural variantiVAR_014493497Q → H. Corresponds to variant dbSNP:rs6530Ensembl.1
Natural variantiVAR_046527581T → A. Corresponds to variant dbSNP:rs34922269EnsemblClinVar.1
Natural variantiVAR_020313726T → K1 PublicationCorresponds to variant dbSNP:rs2230018EnsemblClinVar.1
Natural variantiVAR_067226834E → D in a patient with chronic myelomonocytic leukemia. 1 Publication1
Natural variantiVAR_067227922R → K in a patient with chronic myelomonocytic leukemia. 1 Publication1
Natural variantiVAR_0358711106L → R in a colorectal cancer sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF000992 mRNA Translation: AAC51839.1
AF000993 mRNA Translation: AAC51840.1
AC136488 Genomic DNA No translation available.
AL133545 Genomic DNA No translation available.
AL138744 Genomic DNA No translation available.
CH471141 Genomic DNA Translation: EAW59368.1
BC093868 mRNA Translation: AAH93868.1
BC113381 mRNA Translation: AAI13382.1
CCDSiCCDS14265.1
PIRiT02255
RefSeqiNP_066963.2, NM_021140.3
UniGeneiHs.522616

Genome annotation databases

EnsembliENST00000377967; ENSP00000367203; ENSG00000147050
GeneIDi7403
KEGGihsa:7403
UCSCiuc004dge.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF000992 mRNA Translation: AAC51839.1
AF000993 mRNA Translation: AAC51840.1
AC136488 Genomic DNA No translation available.
AL133545 Genomic DNA No translation available.
AL138744 Genomic DNA No translation available.
CH471141 Genomic DNA Translation: EAW59368.1
BC093868 mRNA Translation: AAH93868.1
BC113381 mRNA Translation: AAI13382.1
CCDSiCCDS14265.1
PIRiT02255
RefSeqiNP_066963.2, NM_021140.3
UniGeneiHs.522616

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3AVRX-ray1.80A880-1401[»]
3AVSX-ray1.85A880-1401[»]
ProteinModelPortaliO15550
SMRiO15550
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113246, 35 interactors
CORUMiO15550
DIPiDIP-46192N
IntActiO15550, 19 interactors
MINTiO15550
STRINGi9606.ENSP00000367203

Chemistry databases

BindingDBiO15550
ChEMBLiCHEMBL2069164
GuidetoPHARMACOLOGYi2684

PTM databases

iPTMnetiO15550
PhosphoSitePlusiO15550

Polymorphism and mutation databases

BioMutaiKDM6A

Proteomic databases

EPDiO15550
MaxQBiO15550
PaxDbiO15550
PeptideAtlasiO15550
PRIDEiO15550
ProteomicsDBi48752

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000377967; ENSP00000367203; ENSG00000147050
GeneIDi7403
KEGGihsa:7403
UCSCiuc004dge.5 human

Organism-specific databases

CTDi7403
DisGeNETi7403
EuPathDBiHostDB:ENSG00000147050.14
GeneCardsiKDM6A
GeneReviewsiKDM6A
H-InvDBiHIX0019137
HGNCiHGNC:12637 KDM6A
HPAiHPA000568
HPA001165
HPA002111
MalaCardsiKDM6A
MIMi300128 gene
300867 phenotype
neXtProtiNX_O15550
OpenTargetsiENSG00000147050
Orphaneti2322 Kabuki syndrome
PharmGKBiPA37262
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1124 Eukaryota
KOG1246 Eukaryota
COG0457 LUCA
GeneTreeiENSGT00410000025758
InParanoidiO15550
KOiK11447
PhylomeDBiO15550
TreeFamiTF317405

Enzyme and pathway databases

ReactomeiR-HSA-3214842 HDMs demethylate histones
R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogenesis

Miscellaneous databases

ChiTaRSiKDM6A human
GeneWikiiUTX_(gene)
GenomeRNAii7403
PROiPR:O15550
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000147050 Expressed in 223 organ(s), highest expression level in kidney
CleanExiHS_UTX
ExpressionAtlasiO15550 baseline and differential
GenevisibleiO15550 HS

Family and domain databases

Gene3Di1.25.40.10, 2 hits
InterProiView protein in InterPro
IPR003347 JmjC_dom
IPR029516 KDM6C
IPR013026 TPR-contain_dom
IPR011990 TPR-like_helical_dom_sf
IPR019734 TPR_repeat
PANTHERiPTHR14017:SF9 PTHR14017:SF9, 2 hits
PfamiView protein in Pfam
PF02373 JmjC, 1 hit
PF13181 TPR_8, 1 hit
SMARTiView protein in SMART
SM00558 JmjC, 1 hit
SM00028 TPR, 6 hits
SUPFAMiSSF48452 SSF48452, 2 hits
PROSITEiView protein in PROSITE
PS51184 JMJC, 1 hit
PS50005 TPR, 7 hits
PS50293 TPR_REGION, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiKDM6A_HUMAN
AccessioniPrimary (citable) accession number: O15550
Secondary accession number(s): Q52LL9, Q5JVQ7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: September 23, 2008
Last modified: November 7, 2018
This is version 182 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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